T cell cytolytic capacity is independent of initial stimulation strength.
View / Open Files
Authors
Richard, Arianne C
Göttgens, Berthold
Publication Date
2018-08Journal Title
Nat Immunol
ISSN
1529-2908
Publisher
Springer Science and Business Media LLC
Volume
19
Issue
8
Pages
849-858
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Richard, A. C., Lun, A. T., Lau, W. W., Göttgens, B., Marioni, J. C., & Griffiths, G. M. (2018). T cell cytolytic capacity is independent of initial stimulation strength.. Nat Immunol, 19 (8), 849-858. https://doi.org/10.1038/s41590-018-0160-9
Abstract
How cells respond to myriad stimuli with finite signaling machinery is central to immunology. In naive T cells, the inherent effect of ligand strength on activation pathways and endpoints has remained controversial, confounded by environmental fluctuations and intercellular variability within populations. Here we studied how ligand potency affected the activation of CD8+ T cells in vitro, through the use of genome-wide RNA, multi-dimensional protein and functional measurements in single cells. Our data revealed that strong ligands drove more efficient and uniform activation than did weak ligands, but all activated cells were fully cytolytic. Notably, activation followed the same transcriptional pathways regardless of ligand potency. Thus, stimulation strength did not intrinsically dictate the T cell-activation route or phenotype; instead, it controlled how rapidly and simultaneously the cells initiated activation, allowing limited machinery to elicit wide-ranging responses.
Keywords
CD8-Positive T-Lymphocytes, Cell Line, Animals, Mice, Inbred C57BL, Mice, Receptors, Antigen, T-Cell, alpha-beta, RNA, Lymphocyte Activation, Signal Transduction, Cytotoxicity, Immunologic, Genome, Single-Cell Analysis
Sponsorship
Wellcome Trust (103930/Z/14/Z)
Medical Research Council (MR/P014178/1)
Leukaemia & Lymphoma Research (12029)
Cancer Research UK (21762)
Cancer Research UK (C14303/A17197)
Medical Research Council (MC_PC_12009)
Wellcome Trust (100140/Z/12/Z)
Medical Research Council (MR/M008975/1)
Identifiers
External DOI: https://doi.org/10.1038/s41590-018-0160-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279751
Rights
Licence:
http://www.rioxx.net/licenses/all-rights-reserved
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.